The objectives of the proposed research are: (1) to determine if some of the minor histocompatibility alloantigens expressed on mouse epidermal cells represent unique, tissue-specific determinants of cellular immunity; (2) to characterize the genetic control and major histocompatibility complex restriction of the cell-mediated cytotoxicity evoked by these antigens; and (3) to determine if these antigens are responsible for the unusual volnerability of skin allografts to transplantation immunity. To accomplish these objectives, we propose to isolate clones of cytotoxic T-lymphocytes generated by immunization with allogeneic epidermal cells in H-S haplotype-identical strain combinations, and to maintain them in continuous culture with the use of T-cell growth factor. The specificity of the monoclonal effector cells would be determined in vitro by cold target inhibition, hot-pulse suicide and monolayer adsoption techniques, and their ability to mediate specific skin allograft rejection would be determined in vivo in adoptive transfer and negative selection experiments. The cytotoxic T-lymphocyte clones would be used to determine the polymorphism of epidermal cell allo-antigens and also as immunogens to induce anti-idiotypic reactions that might modulate skin allograft rejection.